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Molecular & Cellular Proteomics 5:462-483, 2006.
© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Apocrine Cysts of the Breast

Biomarkers, Origin, Enlargement, and Relation with Cancer Phenotype^*

Julio E. Celis^,,¶, Pavel Gromov^,, José M. A. Moreira^,, Teresa Cabezón^,, Esbern Friis^,||, Ilse M. M. Vejborg^,**, Gottfried Proess^,, Fritz Rank^, and Irina Gromova^,

From the Danish Centre for Translational Breast Cancer Research (DCTB) and Department of Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, ^|| Department of Breast and Endocrine Surgery, ^** Radiology Department, Mammography Division, and Department of Pathology, the Centre of Diagnostic Investigations, Rigshospitalet, DK-2100 Copenhagen, Denmark and Eurogentec, Parc Scientifique du Sart Tilman, 4102 Seraing, Belgium

Up to one-third of women aged 30–50 years have cysts in their breasts and are presumed to be at increased risk of developing breast cancer. Here we present an extensive proteomic and immunohistochemistry (IHC) study of breast apocrine cystic lesions aimed at generating specific biomarkers and elucidating the relationship, if existent, of apocrine cysts with cancer phenotype. To this end we compared the expression profiles of apocrine macrocysts obtained from mastectomies from high risk cancer patients with those of cancerous and non-malignant mammary tissue biopsies collected from the same patients. We identified two biomarkers, 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase, that were expressed specifically by apocrine type I cysts as well as by apocrine metaplastic cells in type II microcysts, terminal ducts, and intraductal papillary lesions. No expression of these markers was observed in non-malignant terminal ductal lobular units, type II flat cysts, stroma cells, or fat tissue as judged by IHC analysis of matched non-malignant tissue samples collected from 93 high risk patients enrolled in our cancer program. IHC analysis of the corresponding 93 primary tumors indicated that most apocrine changes have little intrinsic malignant potential, although some may progress to invasive apocrine cancer. None of the apocrine lesions examined, however, seemed to be a precursor of invasive ductal carcinomas, which accounted for 81% of the tumors analyzed. Our studies also provided some insight into the origin, development, and enlargement of apocrine cysts in mammary tissue. The successful identification of differentially expressed proteins that characterize specific steps in the progression from early benign lesions to apocrine cancer opens a window of opportunity for designing and testing new approaches for pharmacological intervention, not only in a therapeutic setting but also for chemoprevention, to inhibit cyst development as both 15-hydroxyprostaglandin dehydrogenase and 3-hydroxymethylglutaryl-CoA reductase are currently being targeted for chemoprevention strategies in various malignancies.

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				J. E. Celis, P. Gromov, T. Cabezon, J. M. A. Moreira, E. Friis, K. Jirstrom, A. Llombart-Bosch, V. Timmermans-Wielenga, F. Rank, and I. Gromova 15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma Mol. Cell. Proteomics, October 1, 2008; 7(10): 1795 - 1809. [Abstract] [Full Text] [PDF]